PB1930: EPIC: A NON-INTERVENTIONAL, OBSERVATIONAL STUDY OF CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS TREATED WITH FIRST-LINE ACALABRUTINIB THROUGH THE UK EARLY ACCESS PROGRAMME. INTERIM ANALYSIS UP TO 24 MONTHS
Authors: Toby Eyre, Nicolas Martinez-Calle, Renata Walewska, Joe Hickey, Betina Blak, Anna Pickin, Sukhjit Hunjan, Orlaith Condon, Satoshi Hori
Journal: HemaSphere (2023)

Topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical Background: Clinical trials of acalabrutinib, a second-generation Bruton’s tyrosine kinase inhibitor, show high response rates and an acceptable safety profile in patients with chronic lymphocytic leukemia (CLL). However, there is a lack of real-world data on the use of acalabrutinib in the first-line treatment of CLL. Aims: To present an interim analysis (IA) of the baseline demographics, clinical characteristics, and treatment patterns of patients with CLL up to 24 months post-initiation of first-line acalabrutinib via the UK Early Access Programme (EAP). Methods: This is a retrospective multi-centre cohort study involving data collection from medical records (ClinicalTrials.gov: NCT05557695). Eligible patients were treatment-naïve CLL patients who initiated acalabrutinib between 1st April 2020 and 1st April 2021 as part of the EAP and were recruited from 5 sites in England for this IA. Data collected included baseline clinical and demographic characteristics, and acalabrutinib treatment patterns. This study has planned follow-up of up to 60 months from the date of acalabrutinib start (index date). Data cut for this IA was 23rd January 2023. Results: This IA includes 54 patients. Median age at index was 74.5 years (Interquartile range (IQR), 69.0–78.6); 59% (32/54) of patients were male, 84% (43/51) were White British. 88% (36/41) of patients had an Eastern Cooperative Oncology Group performance score of 0-1 and 12% (5/41) had a score of 2 (13 had no score recorded); the median Cumulative Illness Rating Scale-Geriatric (CIRS-G) score at index was 2.0 (IQR, 0.0–4.0; n=15). At index, 53% (20/38) of patients had creatinine clearance <60 mL/min. 7% (4/54) of patients had a confirmed ATM mutation, 6% (3/54) had a confirmed TP53 mutation, 2% (1/54) of patients had a confirmed IGHV mutation (≥2% difference from germline), and none had a chromosome 17p13.1 deletion. Median time between CLL diagnosis and index was 3.1 years (IQR, 1.4–7.3). The median duration of follow up was 27.4 months (IQR, 24.6–29.9); 87% (47/54) and 76% (41/54) of patients had durations of observation ≥1 year and ≥2 years, respectively. 1 patient received a reduced daily dose of acalabrutinib (100 mg) at initiation. 43 patients remained on treatment at 12 months, 10 had discontinued (1 patient not recorded). The continuation rate at 12 months was 81.1% (95% CI, 71.3%–92.4%; n=53). Of 54 patients with relevant medical records at the time of data cut, 28% (15/54) had discontinued acalabrutinib. Of the 14 recorded reasons given for treatment discontinuation, 64% (9/14) were due to adverse events, 7% (1/14) were patient decision and 29% (4/14) other; no discontinuations were recorded due to progressive disease. The median real-world overall time on treatment (n=53; up to 12 months) was 12.0 months (IQR, 11.6–12.0). Of 27 patients with relevant medical records, 70% (19/27) had a recorded diagnosis of COVID-19; of these, 89% (17/19) had diagnoses confirmed via a test. The most common treatment received for COVID-19 (for 32% of patients; 6/19) was sotrovimab. Overall at the time of data cut, 20% (5/25) of patients had received up to their 6th COVID-19 vaccination dose, 28% (7/25) their fifth, 4% (1/25) their fourth, 24% (6/25) their third, 4% (1/25) their 2nd and 12% (3/25) their first; 1 patient had had no vaccine (29 patients had no record). Summary/Conclusion: This first IA shows an 81.1% (95% CI, 71.3%–92.4%; n=53) acalabrutinib real-world continuation rate at 12 months in treatment-naïve patients with CLL. Future analyses are aiming at including retrospective data from around 40 clinical sites with approximately 350 eligible patients. Keywords: Chronic lymphocytic leukemia, Real world data